The Cholecystectomy As A Day Case (CAAD) Score: A Validated Score of Preoperative Predictors of Successful Day-Case Cholecystectomy Using the CholeS Data Set.

BACKGROUND: Day-case surgery is associated with significant patient and cost benefits. However, only 43% of cholecystectomy patients are discharged home the same day. One hypothesis is day-case cholecystectomy rates, defined as patients discharged the same day as their operation, may be improved by better assessment of patients using standard preoperative variables. METHODS: Data were extracted from a prospectively collected data set of cholecystectomy patients from 166 UK and Irish hospitals (CholeS). Cholecystectomies performed as elective procedures were divided into main (75%) and validation (25%) data sets. Preoperative predictors were identified, and a risk score of failed day case was devised using multivariate logistic regression. Receiver operating curve analysis was used to validate the score in the validation data set. RESULTS: Of the 7426 elective cholecystectomies performed, 49% of these were discharged home the same day. Same-day discharge following cholecystectomy was less likely with older patients (OR 0.18, 95% CI 0.15-0.23), higher ASA scores (OR 0.19, 95% CI 0.15-0.23), complicated cholelithiasis (OR 0.38, 95% CI 0.31 to 0.48), male gender (OR 0.66, 95% CI 0.58-0.74), previous acute gallstone-related admissions (OR 0.54, 95% CI 0.48-0.60) and preoperative endoscopic intervention (OR 0.40, 95% CI 0.34-0.47). The CAAD score was developed using these variables. When applied to the validation subgroup, a CAAD score of ≤5 was associated with 80.8% successful day-case cholecystectomy compared with 19.2% associated with a CAAD score >5 (p < 0.001). CONCLUSIONS: The CAAD score which utilises data readily available from clinic letters and electronic sources can predict same-day discharges following cholecystectomy.

Obesity-related insulin resistance: implications for the surgical patient.

In healthy surgical patients, preoperative fasting and major surgery induce development of insulin resistance (IR). IR can be present in up to 41% of obese patients without diabetes and this can rise in the postoperative period, leading to an increased risk of postoperative complications. Inflammation is implicated in the aetiology of IR. This review examines obesity-associated IR and its implications for the surgical patient. Searches of the Medline and Science Citation Index databases were performed using various key words in combinations with the Boolean operators AND, OR and NOT. Key journals, nutrition and metabolism textbooks and the reference lists of key articles were also hand searched. Adipose tissue has been identified as an active endocrine organ and the chemokines secreted as a result of macrophage infiltration have a role in the pathogenesis of IR. Visceral adipose tissue appears to be the most metabolically active, although results across studies are not consistent. Results from animal and human studies often provide conflicting results, which has rendered the pursuit of a common mechanistic pathway challenging. Obesity-associated IR appears, in part, to be related to inflammatory changes associated with increased adiposity. Postoperatively, the surgical patient is in a proinflammatory state, so this finding has important implications for the obese surgical patient.

Salivary and urinary assessment of fluoride and silver ion concentrations after silver diamine fluoride application in children: a prospective cohort study.

PURPOSE: The purpose of the study was to determine the fluoride (F) and silver (Ag) ions levels in the saliva and urine of healthy children after silver diamine fluoride (SDF) application on dental carious lesions. METHODS: Sixty children (4-6 years with ≥ 3 caries lesions) were recruited from the outpatient department of Pediatric Dentistry. From each child, 3 ml unstimulated saliva samples were collected at baseline, one hour, and 24 h after SDF application. Similarly, 3 ml urine samples were collected prior to and after 24 h of SDF application. F and Ag ion concentrations were determined by fluoride ion-selective electrode (ISE) and inductively coupled plasma mass spectrometry (ICPMS), respectively. RESULTS: The mean ± standard deviation (SD) baseline, 1-h, and 24-h salivary F concentrations (ppm) were 0.07 ± 0.07, 0.93 ± 0.48, and 0.19 ± 0.19, respectively, while the mean baseline and 24-h urinary F concentrations (ppm) were 0.33 ± 0.20 ppm and 0.43 ± 0.25 ppm, respectively. The mean baseline, 1-h, and 24-h salivary Ag concentrations (ppb) were 4.22 ± 3.15, 4198 ± 350, and 56.93 ± 37, respectively. The mean baseline and 24-h urinary Ag concentrations (ppb) were 2.80 ± 2.93 ppb and 4.72 ± 4.0 ppb, respectively. There were statistically elevated F and Ag ion concentrations at 1 h and 24 h after SDF application as compared to the baseline. CONCLUSION: Salivary and urinary F and Ag ions concentrations elevated significantly at 24 h following SDF applications in children. A significant high recovery of these ions in urine indicates minimal systemic absorption, thus intermittent topical application of 38% SDF has a minimal risk of toxicity.

Bilateral fusion in primary mandibular teeth: a report of two cases.

The rare anomaly of fusion in primary dentition has very little documentation in Indian population. Two rare cases of bilateral fusion between primary mandibular lateral incisors and canines and primary mandibular central incisors and lateral incisors have been presented in this report. A minimal intervention approach, preventive procedures, and a long-term follow-up have been discussed.

microRNA-21 ameliorates the impairment of autophagy in palatal wound healing.

Fibroblast injury and autophagy dysfunction have been shown to contribute to the persistence of oral wounds. Recently, microRNAs have emerged as vital regulators and fine tuners of various pathophysiological cellular processes that influence the wound healing process. This study explored the biological function and regulatory mechanism of miRNA-21 (miR-21) in the healing of oral wounds by interfering with autophagy. Healthy gingival cells derived from wild-type (WT) and from miR-21KO mice were characterized by immunocytofluorescence, and changes in wound healing were subsequently assessed using an in vitro scratch wound healing assay. The roles of critical proteins required for autophagy, autophagy related 5 (ATG5) and Bcl-2 interacting coiled-coil protein 1 (Beclin1) were evaluated by immunohistochemistry. Human gingival fibroblasts (HGFs) were transfected with a miR-21 mimic and a miR-negative control, and the relative expression of miR-21, ATG5, Beclin1 and LC3-I/II was characterized by qRT-PCR and Western blot. Pathological changes were observed in a palatal wound healing model using WT and miR-21KO mice. Immunohistochemistry was used to examine extracellular matrix (ECM) proteins and autophagy markers. Cell migration was delayed in gingiva-derived mesenchymal stem cells (GMSCs) from miR-21KO mice compared with WT mice. The expression of ATG5 and Beclin1 was significantly up-regulated in miR-21KO gingiva. Transfection of a miR-21 mimic into HGFs inhibited autophagy and up-regulated miR-21 expression. Knockdown of miR-21 suppressed the expression of fibronectin and CTGF, enhanced the autophagy effect of fibroblasts, suggesting that autophagy is involved in miR-21 regulated palatal wound healing. Taken together, these results suggest that miR-21 promotes oral wound healing by increasing ECM production through the inhibition of autophagy and facilitates clinical management of wound healing.

Oral toxicity to high level sodium fluoride causes impairment of autophagy.

Autophagy is a highly conserved intracellular digestion process that degrades damaged proteins and organelles but the biological roles of autophagy in pathological aspects of oral tissues remain largely unknown. We sought to elucidate the function of autophagy, especially its interplay with apoptosis and oxidative stress, in the oral toxicity induced by exposure to 5 mM sodium fluoride (NaF). Human cementoblasts (HCEM-2) in culture were exposed to 5 mM NaF for 5 min, after which cell viability and cell apoptosis were assessed using the MTS assay and an Annexin V-FITC/PI apoptosis detection kit, respectively. Quantitative RT-PCR and Western blotting were performed to characterize the expression levels of markers for autophagy, apoptosis, and oxidative stress. Senescence-resistant (SAMR1) mice were exposed to 5 mM NaF in their drinking water from 12 to 58 weeks. Micro-computed tomography was used to measure changes in their alveolar bone while immunohistochemistry and immunofluorescence staining was used to evaluate protein expression levels. HCEM-2 cells exposed to 5 mM NaF had decreased levels of autophagy, as shown by reduced expression levels of ATG5, Beclin-1 and LC3-II, elicited apoptosis, which in turn induced oxidative stress and inflammation, as manifested by elevated levels of Bax, cleaved caspase-3, SOD1 and phospho NF-κB. Treatment of mice with 5 mM NaF resulted in histological abnormalities in periodontal tissues, induced excessive oxidative stress and apoptosis, and reduced autophagy. Micro-computed tomography analysis demonstrated that 5 mM NaF caused a decrease in bone areas of mice compared with controls. Exposure to 5 mM NaF induced RANKL (receptor activator of nuclear factor κB ligand) and cathepsin K expression in periodontal tissues, while ATG5 and Beclin-1 expression was abrogated by 5 mM NaF. Taken together, our findings suggest that 5 mM NaF elicits oral toxicity that contributes to excessive apoptosis, oxidative stress, and defective autophagy, which aggravates periodontal tissue damage.

In vitro and in vivo evidence for lack of endovascular remodeling by third trimester trophoblasts.

The placental-decidual interaction through invading trophoblasts determines whether a physiological transformation of the uterine spiral arteries is established or not. Trophoblast-orchestrated artery remodeling is central to normal placentation. Dysregulated uteroplacental interaction and vascular remodeling are thought to be associated with the molecular events underlying the pathology of late pregnancy anomalies including preeclampsia. Although the exact gestational age at which trophoblast invasion ceases is not known, it remains unclear whether late pregnancy trophoblasts retain the ability to transform the uterine arteries. Here, we have developed a dual cell, in vitro culture system that mimics the vascular remodeling events during normal pregnancy. We demonstrate that first and third trimester trophoblasts respond differentially to interactive signals from endothelial cells when cultured on matrigel. Term primary trophoblasts or immortalized third trimester extravillous TCL1 trophoblasts not only fail to respond to signals from endothelial cells but also inhibit endothelial cell tube formation. In contrast, HTR8 cells, representing a first trimester trophoblast cell line with invasive properties, undergo spontaneous migration and synchronize with the endothelial cells in a capillary network. This disparity in behavior was confirmed in vivo using a matrigel plug assay. Poor expression of VEGF C and VEGF receptors coupled with high E-cadherin expression by term primary trophoblasts and TCL1 cells contributed to their restricted interactive and migratory properties. We further show that the kinase activity of VEGF R2 is essential for proactive crosstalk by HTR8 cells. This unique behavior of first trimester trophoblasts in the presence of endothelial cells offers a potential approach to study cell-cell interactions and to decipher modulatory components in the serum samples from adverse pregnancy outcomes.

Isolation of bluetongue virus-1 from cattle in India and phylogenetic analysis of the complete coding sequence of the segment-2 gene.

The isolation of BTV-1 serotype from cattle in India and its phylogenetic relationship based on VP2 gene has been reported. Virus (JBP42/12/Ind) is isolated in BHK-21 cell line from blood sample tested positive for BTV antigen in sandwich ELISA from asymptomatic cattle. Full length VP2 gene of cattle isolate was amplified, cloned and sequenced. On BLAST analysis virus isolate was identified as BTV-1 serotype. Phylogenetic tree based on complete VP2 coding region segregated Indian isolates, Australian isolates and African/European isolates in three distinct clusters. Segregation of Indian BTV-1 isolates at close proximity to the monophyletic cluster of Australian BTV-1 isolates indicates the present isolate as "eastern topotype' of BTV. Multiple alignments of VP2 gene nucleotide sequences suggest that, Indian BTV-1 isolate is more closely related to Australian BTV-1 isolates; where 14.1% to 14.4% and 6.8% to 7.4% divergence was observed at nucleotide and deduced amino acid sequence level respectively.

Current status of malaria control.

Malaria caused by Plasmodium parasites kills approximately 1-3 million people and causes disease in 300-500 million people annually throughout the world. The current approaches to curtail this disease include vector control, vaccination, immunotherapy and chemotherapy. The vector control is achieved by reducing vector density, interrupting their life cycle, and creating a barrier between the human host and mosquitoes. A number of vaccine candidates are being clinically tried and R&D effort in this direction is coming in a big way. Currently there are only limited safe drugs for the treatment of this disease, however, reports of emerging resistance against existing drugs warrant the introduction of new drugs, which are unlikely to come from pharmaceutical industries because of limited commercial opportunities. One of the most important current approaches to develop new drugs involves the synthesis of chemical libraries and evaluate them against most validated biochemical targets of malarial parasite. Although a number of such targets in antimalarial drug development are known today, yet only validated and selective biochemical targets including mitochondrial transport, glycolic pathway, folate pathway, proteases and heme metabolism, apicoplast metabolism, glycophospatidyl inositol, lipid metabolism (glycerophospholipids), peptidyl deformylase and oxidative stress in parasite-infected erythrocytes have been discussed here. The well known antimalarial drugs and different drug combinations for the treatment of malaria are also briefly reviewed. A survey of the recently discovered new molecules active against malaria has also been narrated. Lastly, the future of malaria chemotherapy and new directions emerging from literature has been elucidated.

Synthesis and antimycobacterial activities of glycosylated amino alcohols and amines.

Reduction of glycosyl beta-amino esters (6-14 and 25-30) with lithium aluminum hydride resulted in glycosyl amino alcohols (15-23 and 31-36) in good yields. However, reductive amination of glycosyl aldehydes (1-3) with different amines in presence of sodium borohydride resulted in good to moderate yields of glycosyl amines (37-41). All the compounds were evaluated for antitubercular activity against Mycobacterium tuberculosis H37Ra and H37Rv. Compounds 18, 21, 35 and 36 exhibited antitubercular activities with MIC ranging from 6.25 to 3.12 microg ml(-1).

PET-CT offers accurate assessment of tumour length in oesophageal malignancy.

INTRODUCTION: Radiotherapy is increasingly used for both curative and palliative treatment of oesophageal malignancy. Accurate treatment depends on determining tumour location and length. This study assessed the value of PET-CT versus other staging modalities in determining tumour length. MATERIALS AND METHODS: Oesophageal cancer patients who underwent staging with PET/CT and endoscopic ultrasound (EUS) in addition to their diagnostic upper GI endoscopy and subsequent surgical resection were assessed. PET/CT length was obtained retrospectively by using Hermes Hybrid Viewer™ with a 1-5 Standardised Uptake Value grey scale. An SUV of 5 was used as the cut off for determining length. Direct measurement by EUS and OGD were determined. RESULTS: 53 patients underwent PET-CT, EUS, OGD and surgical resection for oesophageal cancer. Overall the correlation between PET-CT and histopathological length was strongest (Pearson r=0.5977, 95% CI 0.390-0.747) versus EUS (Pearson R=0.5365, 95% CI 0.311-0.705) and OGD (Pearson r=0.1574, 95% CI -0.118 to 0.410). After excluding tumours with a significant chemotherapy response, PET-CT length correlated significantly with histopathological length (R=0.5651, p=0.0005). In comparison, the correlation between histological length and EUS (R=0.4637, p=0.0057) measurement was less significant and this did not correlate with OGD (R=-0.1084, p=0.5417). CONCLUSION: Tumour length estimated by PET-CT correlated most strongly with histopathological length of oesophageal malignancy and is the most accurate determinant of tumour length of all the staging modalities. This suggests a potential role for PET-CT in the planning of radiotherapy and resection, particularly when considering the practical limitations of EUS.

Chylous ascites: Why exercise is bad for you.

INTRODUCTION: The development of chylous ascites is usually associated with trauma, iatrogenic or otherwise. Blunt abdominal trauma producing hyperextension or hyperflexion may cause disruption to lymphatic vessels causing chylous ascites. PRESENTATION OF CASE: This report describes the case of a 38-year-old gentleman who presented to the emergency department with severe abdominal pain after completing a triathlon. As the patient was in severe pain, an abdominal CT was performed which demonstrated a possible mid gut volvulus. Subsequent laparotomy noted a significant volume of intra-abdominal chyle with no other abnormalities. DISCUSSION: This is the first report of chylous ascites occurring without associated abdominal pathology after a period of strenuous exercise. CONCLUSION: Chylous ascites can occur as a result of hyperreflexion and hyperextension injuries sustained during strenuous exercise.

Metastatic carcinoid tumour mimicking cholecystitis, and a rare case of intussusception.

This report describes an acute presentation of obstructive jaundice, with a clinical picture of cholecystitis. A primary carcinoid tumour in the terminal ileum with hepatic secondaries was found to be the cause. Additionally, in the terminal ileum was a closely associated lipoma leading to an ileo-caecal intussusception. There are few such cases in the literature, particularly in the absence of any changes in bowel habit or lower abdominal pain. The majority of cases of intussusception in clinical practice occur in the paediatric population. Of the small numbers (<5%) that occur in adulthood, the underlying aetiology is most commonly a primary adenocarcinoma, with a far smaller number being attributable to lipoma, lymphoma and polyps.

Portal venous gas: is it a premorbid indicator?

A 72-year-old Caucasian man presented with subtle and insidious symptoms of pain in the left iliac fossa and vomiting. The first clinical impression was of diverticulitis but he did not improve with conservative management. An initial contrast tomography (CT) scan demonstrated no diagnostic features. Four days later, a repeat CT scan demonstrated intramural gas in the ascending colon and in the intrahepatic portal venous radicles. There was a thrombus in the superior mesenteric artery with infarction of the caecum and ascending colon. An urgent right hemicolectomy was carried out. Although there was resolution of the thrombus and air in the portal system, the patient died 8 days later from intestinal haemorrhage.

Aluminum phosphide poisoning: effect of correction of severe metabolic acidosis on patient outcome.

Forty patients of aluminum phosphide poisoning who were admitted to the ICU of Sir Sunder Lal Hospital, Banaras Hindu University, were studied. Restlessness, excessive thirst, shock, arrhythmias, tachypnoea, and severe metabolic acidosis were the common clinical findings. Only repeated and full correction with intravenous sodium bicarbonate was able to cope up with the severity and rapidity of acidosis. There was no significant change in blood pressure, pulse rate, and respiratory rate after full correction but gradually pulse and systolic blood pressure settled after ionotropic support in the survivors. There was significant improvement from 30.36% in the case when only half correction was done, as has been the common practice, to 57.5%, when full correction of metabolic acidosis was done.

Synthesis and antitubercular activities of bis-glycosylated diamino alcohols.

Conjugate addition of diamines to glycosyl olefinic esters 1a and 1b followed by reduction of resulting bis-glycosyl beta-amino esters (2-7 and 14-19) with lithium aluminium hydride led to the respective glycosyl amino alcohols (8-13 and 20-25) in moderate to good yields. All the compounds were evaluated for antitubercular activity against Mycobacterium tuberculosis H(37)Ra and H(37)Rv. Few of the compounds exhibited antitubercular activity with MIC as low as 6.25-3.12microg/mL in virulent and avirulent strains. Compound 13 was found to be active against MDR strain and showed mild protection in mice.